DNA microarrays are small dense arrays of DNA probes arranged on a substrate. The probes on the microarrays are arranged in cells, each of which contains only DNA probes derived from a single DNA sequence. When the DNA microarray is exposed to test mRNA of unknown or mixed sequence, the test nucleotides will hybridize or bind to the probes in one of more cells of the array. The test nucleotides will only bind to those probes the sequence of which is complementary to a DNA on the array. By intelligently constructing such DNA microarrays, it now is possible to construct microarrays which can be used to explore the expression patterns of human or animal genes during any number of physiological processes. For example, if a scientist had available a microarray including the complete set of the genes expressed by an organism, the scientist could then test against that array the mRNA produced in cells of various tissues of the organism during development. This would enable the scientist to determine which genes turn on and off when during the development of that tissue of the organism. Similar studies can be imagined to study disease susceptibility or progression.
Obesity is a strong risk factor for the development of Type 2 Diabetes Mellitus, a disease characterized by insulin resistance, relative insulin hyposecretion, and hyperglycemia. In fact, over 80% of individuals with Type 2 Diabetes Mellitus are obese. However, only 10% of individuals who are obese are diabetic. It is still unclear what determines which obese, non-diabetic individuals will transition to diabetes.
In the course of transition from healthy to diabetic, it is common for obese individuals to become insulin resistant. The concept of insulin resistance is that the body becomes less sensitive, or even entirely insensitive, to insulin levels in the blood, and hence the metabolic activities triggered by insulin in normal individuals do not proceed or proceed at lower levels. As a result of that lowered metabolic response, the normal physiological feedback mechanisms cause the pancreas to increase insulin production to compensate for the insensitivity of the response to insulin. As the insulin response continues to decrease, insulin production continues to increase until, it is thought, the insulin producing cells are simply exhausted. Thus the onset of resistance to insulin may serve as a predictor of eventual diabetic disease in an individual.
The Obese mouse model represents a well-studied and accepted animal model for human obesity. These animals are homozygous for a gene, designated ob, which is a nonsense mutant form of the gene encoding leptin, a satiety factor secreted by adipocytes. The ob animals are markedly hyperphagic. However, despite extreme obesity, C57BL/6J (B6) ob/ob mice have only mild transient hyperglycemia. The ob mutation can be introgressed into the BTBR mouse strain to obtain severely diabetic mice. Together, these animals provide a functional animal model for the study of obesity present with or without diabetes.